THE IMMUNOGENIC PROPERTIES OF DRUG-RESISTANT MURINE TUMOR-CELLS DO NOT CORRELATE WITH EXPRESSION OF THE MDR PHENOTYPE

Alterations in the immunogenic properties of tumor cells frequently ac company selection for multiple-drug-resistant (MDR) variants. Therefor e, studies were performed to examine the hypothesis that overexpressio n of membrane P-glycoprotein, commonly observed in MDR tumor cells, is associated with enhanced immunogenic properties. Immunogenicity was d etermined by (a) the ability of drug-sensitive parental UV2237M fibros arcoma cells and drug-resistant UV2237M variant cells to immunize norm al mice against rechallenge with parental tumor cells and (b) the abil ity of normal syngeneic mice to reject cell inocula that caused progre ssive tumor growth in immunocompromised mice. Variant UV2237M cell lin es included subpopulations selected for a six- to ten-fold increase in mRNA for P-glycoprotein and expression of the MDR phenotype (resistan ce to doxorubicin) and cells sensitive to doxorubicin (and no expressi on of MDR properties) but resistant to ouabain. All UV2237M drug-resis tant cells were highly immunogenic in immunocompetent mice, regardless of their MDR phenotype. Additional studies showed that CT-26 murine a denocarcinoma cells, sensitive or resistant to doxorubicin (expressing high levels of P-glycoprotein), injected into normal syngeneic Balb/c mice produced rapidly growing tumors. The data do not demonstrate a c orrelation between the immunogenic properties of drug-resistant tumor cells and the expression of P-glycoprotein.